EFECTO DE LA CEREBROLISINA SOBRE LA LESIÓN NEONATAL DEL HIPOCAMPO VENTRAL: IMPLICACIONES EN LA ESQUIZOFRENIA

Abstract

Neonatal ventral hippocampal lesion (nVHL) in rats has been widely used as a neurodevelopmental model to mimic schizophrenia-like behaviors. Molecular and morphological alterations in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of nVH-lesioned animals suggest developmental reorganization of these structures following neonatal lesions. Cerebrolysin (Cbl) is a peptide mixture with neurotrophic and neuroprotective activity that causes neuronal differentiation and maintains the functional integrity and recovery of the nerve cell. This study sought to determine whether Cbl was capable of reducing behavioral and neuronal alterations in nVHL rats. The behavioral analysis included locomotor activity induced by novel environment and amphetamine, social interaction, and sensoriomotor gating. The morphological evaluation included dendritic analysis by using the Golgi-Cox procedure and stereology to quantify the total cell number in PFC and NAcc. Behavioral data show a reduction in the hyperresponsiveness to novel environment- and amphetamine induced locomotion, with an increase in the total time spent in social interactions and in prepulse inhibition in Cbl-treated nVHL rats. In addition, neuropathological analysis of the limbic regions also showed amelioration of dendritic retraction and spine loss in Cbl treated nVHL rats. Cbl treatment also ameliorated dendritic pathology and neuronal loss in the PFC and NAcc in nVHL rats. Besides, cerebrolysin ameliorated alterations in levels of tyrosine hidroxilase in NAcc Shell in nVHl rats. This study demonstrates that Cbl promotes behavioral improvements and recovery of dendritic neuronal damage in postpubertal nVHL rats and suggests that Cbl may have neurotrophic effects in this neurodevelopmental model of schizophrenia. These findings support the possibility that Cbl has beneficial effects in the management of schizophrenia symptoms.